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Volume 26
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Article
Peer-Review Record

Establishment of a Novel In Vitro and In Vivo Model to Understand Molecular Carcinogenesis of Endometriosis-Related Ovarian Neoplasms

Int. J. Mol. Sci. 2025, 26(5), 1995; https://doi.org/10.3390/ijms26051995
by Hasibul Islam Sohel 1, Tohru Kiyono 2, Umme Farzana Zahan 1, Sultana Razia 3, Masako Ishikawa 1, Hitomi Yamashita 1, Kosuke Kanno 1, Shahataj Begum Sonia 1, Kentaro Nakayama 4,* and Satoru Kyo 1,*
Reviewer 1: Anonymous
Int. J. Mol. Sci. 2025, 26(5), 1995; https://doi.org/10.3390/ijms26051995
Submission received: 10 February 2025 / Revised: 20 February 2025 / Accepted: 24 February 2025 / Published: 25 February 2025
(This article belongs to the Special Issue Molecular Genetics in Ovarian Cancer)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript entitled: " Establishment of a novel in vitro and in vivo model to understand molecular carcinogenesis of endometriosis-related ovarian neoplasms" describes a model that may help to clarify the molecular mechanisms of carcinogenesis and understand their histological diversity and novel molecular targets.

In my opinion teh manuiscript is well oraganized. The material section is well explaned. The results section is understandable and fundamented with results from literature.

For these reasons, the manuscript should be accepted with minor revisions.

Comments:

  • The abbreviations should be described when used for the first time
  • Could the authors use another model for the purpose?

Author Response

We sincerely thank you for taking the time to review this manuscript. Please find the detailed responses below. We appreciate your valuable feedback and suggestions

Questions for General Evaluation

Reviewer’s Evaluation

Response and Revisions

Does the introduction provide sufficient background and include all relevant references?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging the background and references as sufficient.

Are all the cited references relevant to the research?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging the relevance of the cited references.

Is the research design appropriate?

Yes/Can be improved/Must be improved/Not applicable

We appreciate your acknowledgment of the appropriateness of the research design.

Are the methods adequately described?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging the clarity of the methodology.

Are the results clearly presented?

Yes/Can be improved/Must be improved/Not applicable

Thank you for your positive feedback on the presentation of the results.

Are the conclusions supported by the results?

Yes/Can be improved/Must be improved/Not applicable

Thank you for your positive feedback on the robustness of our conclusions.

 

Point-by-point response to Comments and Suggestions for Authors

Comments 1: The abbreviations should be described when used for the first time

Response 1: We appreciate your comment. We have ensured that all abbreviations have been defined both in the main text and at the bottom of the manuscript, as per the IJMS author's instruction.

Comments 2: Could the authors use another model for the purpose?

Response 2: We appreciate your valuable query. The current model was chosen based on its relevance to our research goals; however, we are open to exploring other models if required in future studies.

Reviewer 2 Report

Comments and Suggestions for Authors

The work described in this paper represents an experimental approach to explaining how a benign endometriosis condition could evolve into endometriosis-related ovarian neoplasms (ERONs).

Considering the observed somatic mutations in ERONS, the authors sequentially applied those same mutations to a previously immortalized endometriosis-derived epithelial cell line.

            Throughout the paper, the authors have assessed the genetic and molecular characteristics of the different derivatized cell types following diverse genetic manipulations.

            Both in vitro and in vivo, the sequential addition of genetic alterations conferred to the derived cell types phenotypic characteristics associated to a malignant behavior. In vivo models of xenografts in SCID mice and in Nude mice showed different tumor histological patterns. suggesting a B-cell influence in that difference.

            According to their observations, three specific genetic combinations (ARID1A KO / KRAS MT / overexpressed c-Myc or ARID1A KO / overexpressed AKT / overexpressed c-Myc) are essential drivers for the development of ERONs.

 

            The paper includes a pertinent number of well designed tables and illustrative figures, as well as supplementary materials.

         The authors have already made significant previous contributions on this topic.

 

Minor comments

 

  1. Panels A and B are not labeled in Figure 4.
  2. Sections 4.5. and 4.6.  have the same heading:  Analysis of population doubling. This mistake should be corrected.

Author Response

Thank you for your valuable and constructive review of our manuscript. Please find our detailed responses below, with the corresponding revisions highlighted in the re-submitted files for your consideration.

2. Questions for General Evaluation

Reviewer’s Evaluation

Response and Revisions

Does the introduction provide sufficient background and include all relevant references?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging

the introduction and references.

Are all the cited references relevant to the research?

Yes/Can be improved/Must be improved/Not applicable

Thank you for your positive feedback.

Is the research design appropriate?

Yes/Can be improved/Must be improved/Not applicable

Thank you for your positive assessment of the research design.

Are the methods adequately described?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging the clarity of the methodology.

Are the results clearly presented?

Yes/Can be improved/Must be improved/Not applicable

Thank you for your positive remarks on how the results are presented.

Are the conclusions supported by the results?

Yes/Can be improved/Must be improved/Not applicable

Thank you for acknowledging the validity of our conclusions based on the results.

 

Point-by-point response to Comments and Suggestions for Authors

Comments 1: Panels A and B are not labeled in Figure 4.

Response 1: Thank you for your careful review and pointing out my mistake. The issue was due to an oversight in the figure legend, where Panels A and B were mistakenly included. We have now corrected the legend accordingly while keeping the figure unchanged.

Comments 2: Sections 4.5. and 4.6.  have the same heading: Analysis of population doubling. This mistake should be corrected.

Response 2: We appreciate your thorough review and fully agree with your comments. The repeated section headings have been corrected as suggested.

 

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